Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines

Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporat...

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Veröffentlicht in:Journal of biomedical materials research. Part A 2010-02, Vol.92A (2), p.504-512
Hauptverfasser: Carr, Daniel A., Peppas, Nicholas A.
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Peppas, Nicholas A.
description Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
doi_str_mv 10.1002/jbm.a.32395
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Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. 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Endocrine system ; HT29 Cells ; Humans ; Hydrogels ; Hypoglycemic Agents - administration &amp; dosage ; Hypoglycemic Agents - chemistry ; Insulin ; Insulin - administration &amp; dosage ; Insulin - chemistry ; Intestinal Mucosa - metabolism ; Kinetics ; Materials Testing ; Medical sciences ; Methylmethacrylates - chemistry ; Microparticles ; Nanoparticles ; oral delivery ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Povidone - chemistry ; Proteins ; Proteins - administration &amp; dosage ; Reproduction ; Transport</subject><ispartof>Journal of biomedical materials research. 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Part A</title><addtitle>J. Biomed. Mater. Res</addtitle><description>Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</description><subject>Administration, Oral</subject><subject>Algorithms</subject><subject>Assessments</subject><subject>Biological and medical sciences</subject><subject>Caco-2 Cells</subject><subject>Carriers</subject><subject>cell culture</subject><subject>Cell Survival - drug effects</subject><subject>Crosslinking</subject><subject>cytocompatibility</subject><subject>Drug Carriers</subject><subject>Drug Delivery Systems</subject><subject>Gastric Mucosa - metabolism</subject><subject>General pharmacology</subject><subject>Hormones. Endocrine system</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Hypoglycemic Agents - administration &amp; dosage</subject><subject>Hypoglycemic Agents - chemistry</subject><subject>Insulin</subject><subject>Insulin - administration &amp; dosage</subject><subject>Insulin - chemistry</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Kinetics</subject><subject>Materials Testing</subject><subject>Medical sciences</subject><subject>Methylmethacrylates - chemistry</subject><subject>Microparticles</subject><subject>Nanoparticles</subject><subject>oral delivery</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. 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Endocrine system</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Hypoglycemic Agents - administration &amp; dosage</topic><topic>Hypoglycemic Agents - chemistry</topic><topic>Insulin</topic><topic>Insulin - administration &amp; dosage</topic><topic>Insulin - chemistry</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Kinetics</topic><topic>Materials Testing</topic><topic>Medical sciences</topic><topic>Methylmethacrylates - chemistry</topic><topic>Microparticles</topic><topic>Nanoparticles</topic><topic>oral delivery</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carr, Daniel A.</au><au>Peppas, Nicholas A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines</atitle><jtitle>Journal of biomedical materials research. Part A</jtitle><addtitle>J. Biomed. Mater. Res</addtitle><date>2010-02</date><risdate>2010</risdate><volume>92A</volume><issue>2</issue><spage>504</spage><epage>512</epage><pages>504-512</pages><issn>1549-3296</issn><issn>1552-4965</issn><eissn>1552-4965</eissn><abstract>Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19213059</pmid><doi>10.1002/jbm.a.32395</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Administration, Oral
Algorithms
Assessments
Biological and medical sciences
Caco-2 Cells
Carriers
cell culture
Cell Survival - drug effects
Crosslinking
cytocompatibility
Drug Carriers
Drug Delivery Systems
Gastric Mucosa - metabolism
General pharmacology
Hormones. Endocrine system
HT29 Cells
Humans
Hydrogels
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - chemistry
Insulin
Insulin - administration & dosage
Insulin - chemistry
Intestinal Mucosa - metabolism
Kinetics
Materials Testing
Medical sciences
Methylmethacrylates - chemistry
Microparticles
Nanoparticles
oral delivery
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Povidone - chemistry
Proteins
Proteins - administration & dosage
Reproduction
Transport
title Assessment of poly(methacrylic acid-co-N-vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco-2 and HT29-MTX cell lines
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